See King et al. (doi:10.1093/aww348) for a scientific commentary on this article.Detailed mapping of clinical dysfunctions to the cerebellar lobules in disease populations is necessary to establish the functional significance of lobules implicated in cognitive and motor functions in normal subjects. This study constitutes the first quantitative examination of the lobular correlates of a broad range of cognitive and motor phenomena in cerebellar disease. We analysed cross-sectional data from 72 cases with cerebellar disease and 36 controls without cerebellar disease. Cerebellar lobule volumes were derived from a graph-cut based segmentation algorithm. Sparse partial least squares, a variable selection approach, was used to identify lobules associated with motor function, language, executive function, memory, verbal learning, perceptual organization and visuomotor coordination. Motor dysfunctions were chiefly associated with the anterior lobe and posterior lobule HVI. Confrontation naming, noun fluency, recognition, and perceptual organization did not have cerebellar associations. Verb and phonemic fluency, working memory, cognitive flexibility, immediate and delayed recall, verbal learning, and visuomotor coordination were variably associated with HVI, Crus I, Crus II, HVII B and/or HIX. Immediate and delayed recall also showed associations with the anterior lobe. These findings provide preliminary anatomical evidence for a functional topography of the cerebellum first defined in task-based functional magnetic resonance imaging studies of normal subjects and support the hypotheses that (i) cerebellar efferents target frontal lobe neurons involved in forming action representations and new search strategies; (ii) there is greater involvement of the cerebellum when immediate recall tasks involve more complex verbal stimuli (e.g. longer words versus digits); and (iii) it is involved in spontaneous retrieval of long-term memory. More generally, they provide an anatomical background for studies that seek the mechanisms by which cognitive and motor dysfunctions arise from cerebellar degeneration. Beyond replicating these findings, future research should employ experimental tasks to probe the integrity of specific functions in cerebellar disease, and new imaging methods to quantitatively map atrophy across the cerebellum.

Background: Survival in frontotemporal dementia (FTD) is not well understood. We conducted a mixed effects meta-analysis of survival in FTD to examine phenotype differences and contributory factors. Methods: The PubMed, Medline, EMBASE, CINAHL, PsycINFO and Cochrane databases were searched for studies describing survival or natural history of behavioral variant FTD (bvFTD), progressive non-fluent aphasia (PNFA), semantic dementia (SD), FTD with amyotrophic lateral sclerosis (FTD-ALS), progressive supranuclear palsy and corticobasal degeneration. There were no language restrictions. Results: We included 27 studies (2,462 subjects). Aggregate mean and median survival were derived for each phenotype and, for comparison, Alzheimer's disease (AD) (using data from the selected studies). Survival was shortest in FTD-ALS (2.5 years). Mean survival was longest in bvFTD and PNFA (8 years) and median survival in SD (12 years). AD was comparable in survival to all except FTD-ALS. Age and sex did not affect survival; the education effect was equivocal. Heterogeneity in FTD survival was largely, but not wholly, explained by phenotypes. Conclusions: Survival differs for FTD phenotypes but, except for FTD-ALS, compares well to AD survival. Elucidating the potential causes of within-phenotype heterogeneity in survival (such as complicating features and comorbidities) may open up opportunities for tailored interventions.

Mild cognitive executive functions and visual-motor coordination impairments seen in SCA6 patients correlate with decreased resting-state connectivity in the attention network, suggesting a possible metric for the study of cognitive dysfunction in cerebellar disease. Hum Brain Mapp 38:3001-3010, 2017. © 2017 Wiley Periodicals, Inc.